The invention concerns a method for sample preparation for magnetic resonance (=MR) measurements using Hyperpolarization by Dissolution Dynamic Nuclear Polarization, comprising:
1.1) preparation of frozen beads of a first kind containing paramagnetic substances, in particular radicals, in addition to the solute under investigation with suitable, in particular glass-forming solvents;
2.1) insertion of the frozen beads into a polarizing magnet;
3.1) creation of enhanced polarization of nuclei within the sample in a magnetic field at cryogenic temperatures;
4.1) heating of the sample to room temperature;
5.1) transfer of the polarized sample from the polarizing magnet to an MR magnet;
6.1) carrying out an MR measurement. A method as described above is known from US 2006/0173282 A1 and GB 0711048.9.
Dynamic nuclear polarization (DNP) can enhance the nuclear polarization, i.e., the difference between the populations of the Zeeman levels /α> and /β3> of a spin I=½, by up to four orders of magnitude with respect to the Boltzmann distribution at room temperature (Abragam, A.; Goldman, M. Rep. Prog. Phys. 1978, 41, 395-467).
The enhancement of the nuclear spin polarization arises from thermal mixing, which is brought about by microwave saturation of the EPR transitions of stable radicals that must be mixed with the sample under investigation before freezing.
In dissolution-DNP, the sample is usually polarized at low temperatures and moderate magnetic fields (T=1.2 K and B0=3.35 or 5 T in our laboratory) (Comment, A.; van den Brandt, B.; Uffmann, K.; Kurdzesau, F.; Jannin, S.; Konter, J. A.; Hautle, P.; Wenckebach, W. T. H.; Gruetter, R.; van der Klink, J. J. Concepts Magn. Reson. B 2007, 31B, 255-269; Comment, A.; van den Brandt, B.; Uffmann, K.; Kurdzesau, F.; Jannin, S.; Konter, J. A.; Hautle, P.; Wenckebach, W. T.; Gruetter, R.; van der Klink, J. J. Appl. Magn. Reson. 2008, 34, 313-319; Jannin, S.; Comment, A.; Kurdzesau, F.; Konter, J. A.; Hautle, P.; van den Brandt, B.; van der Klink, J. J. J. Chem. Phys. 2008, 128, 241102) and rapidly dissolved (Ardenkjaer-Larsen, J. H.; Fridlund, B.; Gram, A.; Hansson, G.; Hansson, L.; Lerche, M. H.; Servin, R.; Thaning, M.; Golman, K. P Natl Acad Sci USA 2003, 100, 10158-10163) and heated to ambient temperature by a burst of water vapor. To minimize losses of nuclear spin polarization, the transfer from the polarizer to the NMR spectrometer or MRI magnet, including the settling of mechanical vibrations and convection currents, and, if required, the infusion into living organisms, must be completed within an interval T<T1. In our laboratory, the interval T has recently been reduced to 4.5 s.
The radicals in the hyperpolarized solution lead to an increase of the longitudinal relaxation rate R1=1/T1 of the solute, thus limiting the time scales of the dynamic processes that can be monitored with hyperpolarized nuclei. A concomitant enhancement of the transverse relaxation rates R2=1/T2 leads to undesirable line-broadening. The relaxation rates RLLS=1/TLLS of the populations of long-lived states (LLS) (Carravetta, M.; Johannessen, O. G.; Levitt, M. H. Phys. Rev. Lett. 2004, 92, 153003-153007; Carravetta, M.; Levitt, M. H. J. Chem. Phys. 2005, 122, 214505; Pileio, G.; Levitt, M. H. J. Chem. Phys. 2009, 130, 214501; Sarkar, R.; Vasos, P. R.; Bodenhausen, G. J. Am. Chem. Soc. 2007, 129, 328-334) and the decay rates RLLC=1/TLLC of long-lived coherences (LLC) are even more sensitive to the presence of free radicals than populations of eigenstates and single-quantum coherences.
Free radicals tend to be toxic and hyperpolarized solutions should not be infused into living organisms unless the radicals have been eliminated.
Object of the invention is to extend longitudinal and transverse relaxation times in NMR and at the same time eliminate free radicals from hyperpolarized solutions.